Leptin is a powerful stimulant of ventilation in rodents. In humans, resistance
to leptin has been consistently associated with obesity. Raised leptin levels
have been reported in subjects with sleep apnoea or obesity-hypoventilation
syndrome. The aim of the present study was to assess, by multivariate analysis,
the possible association between respiratory centre impairment and levels of
serum leptin. In total, 364 obese subjects (body mass index >or=30 kg.m(-2))
underwent the following tests: sleep studies, respiratory function tests,
baseline and hypercapnic response (mouth occlusion pressure (P(0.1)), minute
ventilation), fasting leptin levels, body composition and anthropometric
measures. Subjects with airways obstruction on spirometry were excluded. Out of
the 346 subjects undergoing testing, 245 were included in the current analysis.
Lung volumes, age, log leptin levels, end-tidal carbon dioxide tension,
percentage body fat and minimal nocturnal saturation were predictors for baseline
P(0.1). The hypercapnic response test was performed by 186 subjects; log leptin
levels were predictors for hypercapnic response in males, but not in females.
Hyperleptinaemia is associated with a reduction in respiratory drive and
hypercapnic response, irrespective of the amount of body fat. These data suggest
the extension of leptin resistance to the respiratory centre.